WT1 gene (Wilms' tumor 1 gene) was identified as a gene responsible for Wilms tumor which is a renal cancer in children (Non-Patent Documents 1 and 2). WT1 is a transcription factor having a zinc finger structure. At the beginning, the WT1 gene was considered to be a tumor suppressor gene. However, subsequent studies (Non-Patent Documents 3, 4, 5 and 6) showed that the WT1 gene rather functions as an oncogene in hematopoietic tumors and solid cancers.
It was shown that a WT1 peptide-specific T-lymphocyte (CTL) can be induced by in vitro stimulating a peripheral blood mononuclear cell with a WT1 peptide, and such a CTL damages a cancer cell such as a hematopoietic tumor cell and solid cancer cell which endogenously expresses WT1. The CTL recognizes the WT1 peptide as the form of the complex in which the WT1 peptide binds to an MHC class I molecule. Therefore, such a WT1 peptide is different depending on the subtypes of MHC class I (Patent Document 1, Non-Patent Document 7, and Patent Documents 2, 3 and 4).
The existence of a helper T cell specific for an cancer antigen is important to induce a CTL effectively (Non-Patent Document 8). The helper T cell is induced and activated by the recognition of a complex of an MHC class II molecule and an antigen peptide on an antigen-presenting cell. The activated helper T cell produces a cytokine such as IL-2, IL-4, IL-5, IL-6 or interferon to help the growth, differentiation or maturation of a B cell. The activated helper T cell also has a function to facilitate the growth, differentiation or maturation of other T cell subsets (for example, Tc and TD cell). Thus, the activated helper T cell has a function to activate an immune system by facilitating the growth or activation of a B cell or T cell. Therefore, enhancing a function of a helper T cell through an MHC class II-binding antigen peptide (a helper peptide) in a cancer immunotherapy to increase the effect of a cancer vaccine is considered to be useful (Non-Patent Document 9). Only a peptide binding to an HLA-DRB1*0401 molecule (Non-Patent Document 10), a peptide binding to an HLA-DRB1*0405 molecule and a peptide binding to an HLA-DRB1*1502 molecule (Patent Document 5) were found as a helper peptide of WT1 to date. Therefore, there is a need to find peptides each biding to an HLA-DRB1*1501, HLA-DPB1*0901 or HLA-DPB1*0501 molecule.
Furthermore, it was shown that among the helper peptides, there is a promiscuous helper peptide which can bind to multiple MHC class II molecules, and induce helper T cells (Non-Patent Documents 11 and 12). However, it was very difficult to identify a promiscuous helper peptide which binds to three or more types of MHC class II molecules and exerts a sufficient effect.    Patent Document 1: WO 2003/106682    Patent Document 2: WO 2005/095598    Patent Document 3: WO 2007/097358    Patent Document 4: International Patent Application No. PCT/JP2007/074146    Patent Document 5: WO 2005/045027    Non-Patent Document 1: Daniel A. Haber et al., Cell. 1990 Jun. 29; 61(7):1257-69.    Non-Patent Document 2: Call K M et al., Cell. 1990 Feb. 9; 60(3):509-20.    Non-Patent Document 3: Menke A L et al., Int Rev Cytol. 1998; 181:151-212. Review.    Non-Patent Document 4: Yamagami T et al., Blood. 1996 Apr. 1; 87(7):2878-84.    Non-Patent Document 5: Inoue K et al., Blood. 1998 Apr. 15; 91(8):2969-76.    Non-Patent Document 6: Tsuboi A et al., Leuk Res. 1999 May; 23(5):499-505.    Non-Patent Document 7: Oka Y et al., Immunogenetics. 2000 February; 51(2):99-107.    Non-Patent Document 8: Gao F G et al., Cancer Res. 2002 Nov. 15; 62(22):6438-41.    Non-Patent Document 9: Zeng G, J Immunother. 2001 May; 24(3):195-204    Non-Patent Document 10: Knights A J et al., Cancer Immunol Immunother. 2002 July; 51(5):271-81.    Non-Patent Document 11: Sotiriadou R et al., Br J Cancer. 2001 Nov. 16; 85(10):1527-34.    Non-Patent Document 12: Hural J A et al., J Immunol. 2002 Jul. 1; 169(1):557-65.